Prevention of Right Heart Failure After Left Ventricular Assist Device Implantation by Phosphodiesterase 5 Inhibitor

Right ventricular (RV) function immediately after left ventricular assist device (LVAD) implantation is a crucial prognostic factor. RV failure is linked to increased mortality and worse outcome. A phosphodiesterase 5 inhibitor, sildenafil, was shown to decrease pulmonary vascular resistance and pulmonary artery pressure post‐LVAD. We report on a series of heart failure patients, and the effect of sildenafil on the incidence of RV failure after LVAD implantation. We retrospectively analyzed the data of end‐stage heart failure patients who underwent LVAD implantation with pulmonary hypertension and RV dysfunction prior to surgery. Patients were divided into two groups; group 1: patients who received sildenafil perioperatively, and group 2: patients who did not receive sildenafil. Hemodynamic and echographic data were collected before and after surgery. Fourteen patients were included, 8 patients in group 1 and 6 in group 2. Sildenafil was administered with a mean dose of 56.2 ± 9.4 mg in group 1 and was able to significantly reduce right heart failure incidence, and to demonstrate a significant reduction in pulmonary vascular resistance, pulmonary artery pressure, transpulmonary gradient, and a significant increase in cardiac output. In conclusion, sildenafil seems to have a promising role perioperatively in preventing acute RV failure postsurgery in patients with RV dysfunction and pulmonary hypertension, requiring LVAD therapy.     

Comparison between short- and long-acting erythropoiesis-stimulating agents in hemodialysis patients: target hemoglobin,variability, and outcome

Purpose

Maintaining target hemoglobin (Hb) with minimal variability is a challenge in hemodialysis (HD) patients. The aim of this study is to compare the long- and short-acting erythropoietin-stimulating agents such as Aranesp and Eprex in achieving these targets.

Methods

Randomized, prospective, open-labeled study of 24 weeks includes stable patients on HD >3 months, age >18 years, and on Eprex for >3 months. Patients were randomized into two groups: A-(Aranesp group):HD patients on Eprex Q TIW or BIW were converted to Aranesp Q weekly, by using the conversion factor of 200:1 and those on Eprex Q weekly to Aranesp Q 2 weeks; B-(Eprex group):patients continued on Eprex treatment. Hemoglobin target was set at (105–125 g/l). Primary end points were percentage of patients achieving target Hb, hemoglobin variability, and number of dose changes in each group.

Results

This study consisted of 139 HD patients: 72 in the Aranesp and 67 in the Eprex—mean (SD) age 54 (16.2) years, 77 (55 %) males. About 46 % were diabetic. Target Hb achieved in 64.8 % of the Aranesp and 59.7 % in the Eprex (p = 0.006). Hb variability was less frequent in the Aranesp group (p = 0.2). Mean number of dose changes was 1.3 (0.87) in the Aranesp and 1.9 (1.2) in the Eprex (p < 0.001). There was 1 vascular access thrombosis in the Aranesp and 8 in the Eprex (p < 0.001). There was no difference in hospitalization and death number between the 2 groups.

Conclusions

Aranesp Q weekly or every 2 weeks is more efficient in achieving target Hb, with less dose changes and minor vascular access complications.     

Improved accuracy of anticoagulant dose prediction using a pharmacogenetic and artificial neural network-based method

Background

The unpredictability of acenocoumarol dose needed to achieve target blood thinning level remains a challenge. We aimed to apply and compare a pharmacogenetic least-squares model (LSM) and artificial neural network (ANN) models for predictions of acenocoumarol dosing.

Methods

LSM and ANN models were used to analyze previously collected data on 174 participants (mean age: 67.45 SD 13.49 years) on acenocoumarol maintenance therapy. The models were based on demographics, lifestyle habits, concomitant diseases, medication intake, target INR, and genotyping results for CYP2C9 and VKORC1. LSM versus ANN performance comparisons were done by two methods: by randomly splitting the data as 50 % derivation and 50 % validation cohort followed by a bootstrap of 200 iterations, and by a 10-fold leave-one-out cross-validation technique.

Results

The ANN-based pharmacogenetic model provided higher accuracy and larger R value than all other LSM-based models. The accuracy percentage improvement ranged between 5 % and 24 % for the derivation cohort and between 12 % and 25 % for the validation cohort. The increase in R value ranged between 6 % and 31 % for the derivation cohort and between 2 % and 31 % for the validation cohort. ANN increased the percentage of accurately dosed subjects (mean absolute error ≤1 mg/week) by 14.1 %, reduced the percentage of mis-dosed subjects (mean absolute error 2-3 mg/week) by 7.04 %, and reduced the percentage of grossly mis-dosed subjects (mean absolute error ≥4 mg/week) by 24 %.

Conclusions

ANN-based pharmacogenetic guidance of acenocoumarol dosing reduces the error in dosing to achieve target INR. These results need to be ascertained in a prospective study.     

Consumer Knowledge,Attitudes and Salt-Related Behavior in the Middle-East: The Case of Lebanon

Sodium intake is high in Lebanon, a country of the Middle East region where rates of cardiovascular diseases are amongst the highest in the world. This study examines salt-related knowledge, attitude and self-reported behaviors amongst adult Lebanese consumers and investigates the association of socio-demographic factors, knowledge and attitudes with salt-related behaviors. Using a multicomponent questionnaire, a cross-sectional study was conducted in nine supermarkets in Beirut, based on systematic random sampling (n = 442). Factors associated with salt-related behaviors were examined by multivariate regression analysis. Specific knowledge and attitude gaps were documented with only 22.6% of participants identifying processed foods as the main source of salt, 55.6% discerning the relationship between salt and sodium, 32.4% recognizing the daily limit of salt intake and 44.7% reporting being concerned about the amount of salt in their diet. The majority of participants reported behavioral practices that increase salt intake with only 38.3% checking for salt label content, 43.7% reporting that their food purchases are influenced by salt content and 38.6% trying to buy low-salt foods. Knowledge, attitudes and older age were found to significantly predict salt-related behaviors. Findings offer valuable insight on salt-related knowledge, attitude and behaviors in a sample of Lebanese consumers and provide key information that could spur the development of evidence-based salt-reduction interventions specific to the Middle East.     

Triclabendazole Effect on Protease Enzyme Activity in the Excretory- Secretory Products of Fasciola hepatica in Vitro

Background

Fasciola hepatica is one of the most important helminthes parasites and triclabendazole (TCBZ) is routinely used for treatment of infected people and animals. Secreted protease enzymes by the F. hepatica plays a critical role in the invasion, migration, nutrition and the survival of parasite and are key targets for novel drugs and vaccines. The aim of study was to determine the protease activity of excretory- secretory products (ESP) of F. hepatica in the presence of TCBZ anthelmintic.

Methods

F. hepatica helminthes were collected and cultured within RPMI 1640 [TCBZ treated (test) and untreated (control)] for 6 h at 37 °C. ESP of treated and control were collected, centrifuged and supernatants were stored at -20°C. Protein concentrations were measured according to Bradford method. Protease enzymes activities of ESP samples were estimated by using sigma’s non-specific protease activity assay. ESP protein bands were detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE).

Results

Mean protein concentrations in control and treated of ESP samples were determined 196.1 ±14.52 and 376.4 ±28.20 μg/ml, respectively. Mean protease enzymes activities in control and treated were 0.37 ±0.1 and 0.089 ±0.03 U/ml, respectively. Significant difference between proteins concentrations and protease enzymes activities of two groups was observed (P<0.05). SDS-PAGE showed different patterns of protein bands between treated and control samples.

Conclusion

The TCBZ reduced secreted protease enzymes activities and possibly effects on invasion, migration, nutrition and particularly survival of the parasite in the host tissues.     

Effect of Sago Starch Modifications on Polystyrene/Thermoplastic Starch Blends

The preparation of polystyrene/thermoplastic starch (PS/TPS) blends was divided into three stages. The first stage involved the preparation of TPS from sago starch. Then, for the second stage, PS was blended with TPS to produce a TPS/PS blend. The ratios of the TPS/PS blend were 20:80, 40:60, 60:40, and 80:20. The final stage was a modification of the composition of TPS/PS blends with succinic anhydride and ascorbic acid treatment. Both untreated and treated blends were characterized by their physical, thermal, and surface morphology properties. The obtained results indicate that modified blends have better tensile strength as the adhesion between TPS and PS was improved. This can be observed from SEM micrographs, as modified blends with succinic anhydride and ascorbic acid had smaller TPS dispersion in PS/TPS blends. The micrograph showed that there was no agglomeration and void formation in the TPS/PS blending process. Furthermore, modified blends show better thermal stability, as proved by thermogravimetric analysis. Water uptake into the TPS/PS blends also decreased after the modifications, and the structural analysis showed the formation of a new peak after the modification process.     

Important Tools for Use by Pediatric Endocrinologists in the Assessment of Short Stature

Assessment and management of children with growth failure has improved greatly over recent years. However, there remains a strong potential for further improvements by using novel digital techniques. A panel of experts discussed developments in digitalization of a number of important tools used by pediatric endocrinologists at the third 360° European Meeting on Growth and Endocrine Disorders, funded by Merck KGaA, Germany, and this review is based on those discussions. It was reported that electronic monitoring and new algorithms have been devised that are providing more sensitive referral for short stature. In addition, computer programs have improved ways in which diagnoses are coded for use by various groups including healthcare providers and government health systems. Innovative cranial imaging techniques have been devised that are considered safer than using gadolinium contrast agents and are also more sensitive and accurate. Deep-learning neural networks are changing the way that bone age and bone health are assessed, which are more objective than standard methodologies. Models for prediction of growth response to growth hormone (GH) treatment are being improved by applying novel artificial intelligence methods that can identify non-linear and linear factors that relate to response, providing more accurate predictions. Determination and interpretation of insulin-like growth factor-1 (IGF-1) levels are becoming more standardized and consistent, for evaluation across different patient groups, and computer-learning models indicate that baseline IGF-1 standard deviation score is among the most important indicators of GH therapy response. While physicians involved in child growth and treatment of disorders resulting in growth failure need to be aware of, and keep abreast of, these latest developments, treatment decisions and management should continue to be based on clinical decisions. New digital technologies and advancements in the field should be aimed at improving clinical decisions, making greater standardization of assessment and facilitating patient-centered approaches.